Calcitonin gene-related peptide (CGRP): role in migraine pathophysiology and therapeutic targeting

Published on Feb 13, 2020in Expert Opinion on Therapeutic Targets5.473
· DOI :10.1080/14728222.2020.1724285
Anne-Sophie Wattiez6
Estimated H-index: 6
(UI: University of Iowa),
Levi P. Sowers10
Estimated H-index: 10
(UI: University of Iowa),
Andrew F. Russo46
Estimated H-index: 46
(UI: University of Iowa)
Sources
Abstract
ABSTRACTIntroduction: The neuropeptide calcitonin gene-related peptide (CGRP) is recognized as a critical player in migraine pathophysiology. Excitement has grown regarding CGRP because of the deve...
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Objective: Characterize the cardiovascular (CV) safety of rimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, in nonclinical assays and clinical trials. Background: Approximately 3.5 million individuals with migraine have had a CV event, condition, or procedure that contraindicates triptan treatment. A single oral 75 mg dose of rimegepant has demonstrated efficacy in 3 Phase 3 trials for the acute treatment of migraine (Studies 301, 302, and 303). Design/Meth...
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Importance Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist under investigation for acute treatment of migraine. Objective To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack. Design, Setting, and Participants Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26,...
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Monoclonal antibodies (mAbs) towards CGRP or the CGRP receptor show good prophylactic antimigraine efficacy. However, their site of action is still elusive. Due to lack of passage of mAbs across the blood-brain barrier the trigeminal system has been suggested a possible site of action because it lacks blood-brain barrier and hence is available to circulating molecules. The trigeminal ganglion (TG) harbors two types of neurons; half of which store CGRP and the rest that express CGRP receptor elem...
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IntroductionThe trigeminal ganglion is unique among the somatosensory ganglia regarding its topography, structure, composition and possibly some functional properties of its cellular components. Be...
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BackgroundUbrogepant is a novel, oral calcitonin gene–related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine. This trial evaluated the safety and tolerability...
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Summary Background Rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist, has shown efficacy in the acute treatment of migraine using a standard tablet formulation. The objective of this trial was to compare the efficacy, safety, and tolerability of a novel orally disintegrating tablet formulation of rimegepant at 75 mg with placebo in the acute treatment of migraine. Methods In this double-blind, randomised, placebo-controlled, multicentre phase 3 trial, adults aged 1...
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Abstract Background Calcitonin gene–related peptide receptor has been implicated in the pathogenesis of migraine. Rimegepant is an orally administered, small-molecule, calcitonin gene–related pepti...
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ABSTRACTIntroduction: The Calcitonin Gene-Related Peptide (CGRP) has been implicated in migraine pathophysiology due to its role in neurogenic inflammation and transmission of trigeminovascular noc...
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Chronic pain remains a major problem worldwide, despite the availability of various non-pharmacological and pharmacological treatment options. Therefore, new analgesics with novel mechanisms of action are needed. Monoclonal antibodies (mAbs) are directed against specific, targeted molecules involved in pain signaling and processing pathways that look to be very effective and promising as a novel therapy in pain management. Thus, there are mAbs against tumor necrosis factor (TNF), nerve growth fa...
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What is known and objectives null Migraine is a disabling disorder that affects individuals of all ages. To date, there are multiple limitations to using guidelines-recommended treatments and preventive therapies. The goal of this review was to provide a comprehensive clinical review of the safety, efficacy and prescribing information of the emerging calcitonin gene-related peptide (CGRP) antagonists. Agents in this new pharmacologic class were approved by the US Food and Drug Administration (FD...
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